Background Prison populations in sub-Saharan Africa (SSA) experience a high burden of disease and poor access to health care. Although it is generally understood that environmental conditions are dire and contribute to disease spread, evidence of how environmental conditions interact with facility-level social and institutional factors is lacking. This study aimed to unpack the nature of interactions and their influence on health and healthcare access in the Zambian prison setting. Methods We conducted in-depth interviews of a clustered random sample of 79 male prisoners across four prisons, as well as 32 prison officers, policy makers and health care workers. Largely inductive thematic analysis was guided by the concepts of dynamic interaction and emergent behaviour, drawn from the theory of complex adaptive systems. Results A majority of inmates, as well as facility-based officers reported anxiety linked to overcrowding, sanitation, infectious disease transmission, nutrition and coercion. Due in part to differential wealth of inmates and their support networks on entering prison, and in part to the accumulation of authority and material wealth within prison, we found enormous inequity in the standard of living among prisoners at each site. In the context of such inequities, failure of the Zambian prison system to provide basic necessities (including adequate and appropriate forms of nutrition, or access to quality health care) contributed to high rates of inmate-led and officer-led coercion with direct implications for health and access to healthcare. Conclusions This systems-oriented analysis provides a more comprehensive picture of the way resource shortages and human interactions within Zambian prisons interact and affect inmate and officer health. While not a panacea, our findings highlight some strategic entry-points for important upstream and downstream reforms including urgent improvement in the availability of human resources for health; strengthening of facility-based health services systems and more comprehensive pre-service health education for prison officers.